It is well-documented that disorders of bone tissues causes numerous significant health problems on a world-wide basis. Because of such significant health problems with bone diseases, numerous efforts have been made to develop new therapeutic agents for bone disorders.
For example, several growth and/or differentiation factors are known to effect bone, cartilage, and dental tissues. Many of these have been evaluated for their ability to speed or alter the healing of defects in these tissues. Such factors include the molecules belonging to the transforming growth factor (TGF) and bone morphogenetic protein (BMP) family as well the epidermal growth factor (EGF), epithelial cell growth factor (ECGF), fibroblast growth factor (FGF), platelet derived growth factor (PDGF), insulin-like growth factor (IGF), and insulin-like growth factor binding protein (IGFBP) families.
Although many of these factors are known to promote proliferation, differentiation, maturation, or mineralization of osteoblastic cells, attempts to develop these factors as novel therapeutics have been limited by their lack of tissue specificity. Administration of these factors affect tissues other than skeletal tissues, which can result in undesirable activities.
For example, the administering of rhBMP-2 to soft tissue (e.g. subcutaneous injection) causes rapid formation of new bone in soft tissue. As a result of this response, use of rhBMP-2 has been limited and needs to be carefully applied in order to prevent calcification in undesirable locations.
A further limitation of using the above growth and/or differentiation factors as a therapeutic is the cost of manufacturing. The factors are all proteins manufactured by recombinant DNA methods, which require large-scale fermentation or cell culture processes. In addition, these manufacturing methods require highly specialized facilities, which further increase the cost of manufacturing. As a result, the manufacturing cost gets translated into a very expensive cost of treatment for using these products.
For example, a locally implantable collagen sponge that contains a BMP family molecule has been used as a medical device for spinal fusion therapies. However, the cost for such a procedure has provided a limitation of its availability to patients who could benefit from this type of treatment.
Accordingly, there is continued interest in the development of new therapeutics that would significantly reduce the cost of treatment. Of particular interest would be a novel therapeutic that would reduce the required dose of the already existing therapeutics.
Furthermore, growth factors other than those in the BMP family, such as those in the TGF, PDGF, EGF, FGF, and IGF families, should be explored as potential therapeutics. The utilization of other growth factors that reduce the efficacious dose and cost of therapies for existing growth factors therapeutics would be of great value to the orthopedic and related medical community and the patients that they serve.